title: Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics.
abstract: Hepatocellular carcinoma has a poor prognosis due to its rapid development and early metastasis. In this report, we characterized the metabolic features of hepatocellular carcinoma using a nontargeted metabolic profiling strategy based on liquid chromatography-mass spectrometry. Fifty pairs of liver cancer samples and matched normal tissues were collected from patients having hepatocellular carcinoma, including tumor tissues, adjacent noncancerous tissues, and distal noncancerous tissues, and 105 metabolites were filtered and identified from the tissue metabolome. The principal metabolic alternations in HCC tumors included elevated glycolysis, gluconeogenesis, and β-oxidation with reduced tricarboxylic acid cycle and Δ-12 desaturase. Furthermore, increased levels of glutathione and other antioxidative molecules, together with decreased levels of inflammatory-related polyunsaturated fatty acids and phospholipase A2, were observed. Differential metabolite levels in tissues were tested in 298 serum specimens from patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Betaine and propionylcarnitine were confirmed to confer good diagnostic potential to distinguish hepatocellular carcinoma from chronic hepatitis and cirrhosis. External validation of cirrhosis and hepatocellular carcinoma serum specimens further showed that this combination biomarker is useful for diagnosis of hepatocellular carcinoma with a supplementary role to α-fetoprotein.
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Yexiong
authors.initials: Y
authors.lastname: Tan
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Yin
authors.forename: Guozhu
authors.initials: G
authors.lastname: Ye
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D001622:Betaine / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D002952:Citric Acid Cycle; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000235:genetics / Q000378:metabolism; D005260:Female; D005943:Gluconeogenesis; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D006521:Hepatitis, Chronic / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D055442:Metabolome / Q000235:genetics*; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; C003223:propionylcarnitine; D001622:Betaine; D044943:Fatty Acid Desaturases; D054467:Phospholipases A2; D005978:Glutathione; D002331:Carnitine